PB2002: ASSOCIATION OF GENE MUTATIONS AND CLINICAL MANIFESTATIONS AND PROGNOSIS IN THE CLINICAL COHORT WITH 218 MDS PATIENTS
Authors: Xue’e Wang, Peixuan Wang, Yan Gu, Yue Hou, Zheng Ge
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: High-throughput testing technologies identified more and more disease-related gene mutations, which deepen the understanding of MDS. Different gene mutations affect the phenotype, development, and prognosis of the disease from different ways. Nowadays, internationally accepted scoring system of MDS includes IPSS、WPSS、IPSS-R, no gene mutation included in these systems. IPSS-M, a new scoring system is proposed in 2022 which considers hematologic parameters and cytogenetic abnormalities, gene mutations, but it did not explain the relationship between IPSS-R and gene mutation, and nor the gene’s effect on clinical symptoms and treatment. More clinical data analysis will help to find out the relevance between gene mutations and clinical characteristics of patients with MDS Aims: In this study, we used the real-world clinical data to find the factors related to the prognosis of MDS patients, to explore whether the combination of IPSS-R classification and gene mutation can better predict the overall survival time(OS) and to identify the correlation between some specific gene mutations and clinical features and drug response in MDS patients. Methods: The clinical data and NGS data of 218 MDS patients from 2013 to 2022 at Zhongda hospital were collected. This study was approved by the Independent Ethics Committee for Clinical Research of Zhongda Hospital Southeast University. SPSS 26.0 statistical software was used for statistical processing. Results: We performed the prognostic analysis in the 218 MDS cohort, and found that age (whether>= 65)、IPSS-R、TP53、DNMT3A、SRSF2、STAG2, and the number of gene mutations have statistical significance with patients’ survival with univariate analysis(table1). While the multivariate analysis showed the age(p=0.004)、TP53(p=0.023), and the grade of IPSS-R(p<0.001) are independent factors for prognosis. We next explored if different gene mutations cause different clinical manifestations and found that TP53(100%) and SF3B1(100%) usually along with anemia, U2AF1 with leukopenia (78.6%), and ASXL1、TP53、RUNX1 always with thrombocytopenia (77.5% 75.0% 78.6%). while TP53 mutated is frequently associated with abnormal chromosome(82.1%). We also observed the survival in low and very low risk IPSS-R group with genetic mutations in ETV6、TP53 and DNMT3A, is similar with that of very high risk of IPSS-R group.(Figure1) Moreover, patients with TET2 mutation are more likely to respond to HMAs. In 130 patients treated with HMAs, 6 of them achieved CR,19 achieved HI, and all of the clinical response patients harbored TET2 mutations. Summary/Conclusion: Our MDS cohort study showed that the patients with older age, higher score of IPSS-R, presence of mutations in gene TP53、DNMT3A、SRSF2、STAG2 have a poor prognosis. Older age、TP53 and IPSS-R are independent prognostic factors. The survival of patients with very low/low risk IPSS-R score patients and ETV6 or TP53 or DNMT3A mutation is similar with that with very high risk of IPSS-R score. Patients with TET2 mutation are more likely to respond to HMAs. Our results indicated the relevance of gene mutations with clinical characteristics of patients with MDS.Figure 1. rvival analysis of M-S group and IPSS-R group and M-S with IPSS-R group (Note:M-S group: very low and low risk patients with ETV6、TP53 and DNMT3A are labeled as higher risk, others as lower risk. j: of very low and low risk of IPSS-R group(75 patients); k: of patients with lower risk and higher risk of M-S group(75 patients); l: of IPSS -R group(218 patients); m:M-S combined with IPSS-R group(218 patients) Keywords: Gene mutation, MDS